Rats, mice, hamster, and monkeys, will be exposed to ozone at concentration in the high ambient range (0.2-0.8 ppm). A multidisciplinary group will make quantitative biochemical, functional and structural evaluations of effects. The findings will have relevance to the specific problem of air pollution and to a general understanding of pulmonary pathobiology. By plotting the relative levels of sensitivity of the various parameters studied and the effects observed, a basis will be provided for making predictions of long-term consequences of photochemical smog on man. Comparison of effects in rats, hamsters, and monkeys will provide for more confident extrapolation to man. This is essential for assessment of air quality criteria. Major aims for the coming five years are to: 1) define mechanisms (antioxidants and heat shock-protein) by which tracheobronchial epithelial populations become resistant to further injury with repeated ozone exposure; 2) define the role of neutrophils in acute lung injury resulting from ozone exposure; 3) examine the effects of long-term ozone exposure on patterns of epithelial cell proliferation during and following exposure; 4) determine the occurrence of ozoneacid aerosol synergy during chronic exposure; 5) identify the long-term significance of changes in collagen structure in fibrotic lungs of ozone-exposed animals and the mechanisms behind these changes; 6) examine the interactive effects of aerosols and particulates on ozone-induced lung injury; and 7) define the pattern of change in centriacinar extracellular matrix during ozone exposure and its role modifying the epithelium.